Accumulating evidence suggests that early life experiences may influence the risk of adult chronic diseases, including cancer. The association between early-life factors and the risk of developing colorectal neoplasia has not been widely studied. Birthweight and body fatness are regulated by insulin and growth factor levels, which are partially determined by genetic variation and partially determined by nutritional status. Although obesity in adulthood has been associated with increased risk of colorectal cancer, data evaluating the association body size in childhood and young adulthood and the risk of colorectal neoplasia are lacking. Colorectal neoplasia includes colorectal carcinoma and the precursor lesion of adenomatous polyps. Several early-life anthropometric measures were previously collected in the two large Harvard cohort studies, the Nurses'Health Study (NHS) (n=121,700 women aged 35-50) and the Health Professionals Follow-up Study (HPFS, n=51,529 men). We propose to comprehensively evaluate the associations of early life body size at different stages: 1) birthweight (666 colorectal cancer cases, 2735 distal adenoma cases);2) body fatness during childhood (1411 colorectal cancer cases, 4475 distal adenoma cases) and 3) body mass index (BMI) at age 18 or 21 (2043 colorectal cancer cases, 5645 distal adenoma cases) with the risk of colorectal cancer and colorectal adenoma. We will evaluate the role of adult weight gain, as well as evaluating whether early-life experience and weight gain are independent of later adult BMI in predicting risk of colorectal cancer. Our study population/sample size is dramatically larger than the few published studies that have evaluated the association between birthweight and colorectal cancer. Moreover, we are proposing the first detailed evaluation of the association between birthweight, early life body size and colorectal adenoma. The NHS and HPFS provide a unique resource for studying these hypotheses because they require many years of follow-up and high quality data. The reduction of childhood obesity is an increasingly important area for public health agencies;if our findings support the hypothesis that factors very early in life contribute significantly to later risk of colorectal cancer and/or adenoma, this could provide additional momentum for interventions targeted at children during the first few years of life. The Principal Investigator is a young researcher, and the proposed grant will be important in facilitating her path towards becoming an independent researcher. PUBLIC HEALTH RELEVANCE: We propose to expand our understanding of the long-term consequences of body size on adult chronic disease by studying the association between early-life anthropometry, birthweight, body size in childhood and young adulthood, and the risk of colorectal neoplasia. The current epidemic of obesity in adults is undeniable;we believe our findings will help generate momentum towards reducing adult obesity by intervening during a critical window of opportunity (e.g. childhood, young adulthood), with the ultimate goal of generating measurable improvements on the burden of colorectal cancer and other chronic diseases.